Allergy and asthma proceedings最新文献

Background: Allergen immunotherapy (AIT) is currently the most effective immunologic form of treatment for patients with atopic allergic diseases commonly used by allergist/immunologists to reduce allergic symptoms by gradually desensitizing the immune system to specific allergens. Currently, the primary mechanism of AIT emphasizes the crucial role of immune regulation, which involves a shift from a T-helper type 2 (Th2) cell response, which promotes allergy, to a T-regulatory (Treg) cell population, which inhibits the allergic inflammatory response through the production of immunosuppressive cytokines interleukin 10 and transforming growth factor β, which play pivotal roles in suppressing the allergic reaction. In a series of previous in vitro and in vivo experiments, we have demonstrated the capacity of synthetic methylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotide (ODN) moieties as well as methylated genomic DNA ODN motifs from Bifidobacterium longum subspecies infantis to activate Treg cell differentiation in contrast to the unmethylated ODN moiety, which promotes proinflammatory responses driven by Th17-mediated responses. Objective: The purpose of the present study was to continue exploring the reciprocally related effects of methylated and unmethylated forms of DNA motifs from B. longum subspecies infantis on inflammation, specifically focusing on evaluating their capacity to alleviate allergic symptoms in a murine allergic disease model. Results: We show that methylated CpG moieties (ODNA) inhibit inflammation by stimulating Treg cells whereas unmethylated CpG moieties (ODNB) promote inflammation through Th1/Th17 pathways. Conclusion: Analysis of our data confirms and extends our previous research on the mechanisms by which methylated and unmethylated forms of DNA motifs influence inflammation. Specifically, the findings demonstrate that methylated CpG moiety (OVA + ODNA) inhibits inflammation by stimulating Treg cells, whereas unmethylated CpG moiety (OVA + ODNB) promotes inflammation through Th1/Th17 pathways. Consequently, these effects were shown to alleviate or to exacerbate allergic symptoms in a murine model of allergic disease. These results set the stage for future clinical trials and studies in humans to explore the therapeutic potential of targeting CpG motifs in the treatment of allergic diseases.

Background: Patients with mast cell activation syndrome (MCAS) can be refractory to standard antimediator therapy. Alternative treatment options to reduce disease burden and improve quality of life are needed. Objective: To compile the evidence that supports the use of omalizumab for patients with refractory MCAS. Methods: Through a systematic review of the PubMed database, we compiled and analyzed the characteristics of patients with refractory MCAS, unresponsive to histamine 1 receptor antihistamines plus another antimediator agent (refractory MCAS), and who were treated with omalizumab. We categorized the clinical response to omalizumab as no, partial, or complete response. Results: We identified nine studies that described a total of 28 patients (median age, 48 years; males, 54%) with refractory MCAS. Twenty-one patients (75%) had nonclonal MCAS, and seven patients (25%) had clonal MCAS. The omalizumab dose ranged from 150 mg every 4 weeks to 300 mg every 3 weeks, with the most common dose being 150 mg every 2 weeks. Most patients had a partial response (61%), and five patients achieved a complete response. Omalizumab was successful in ameliorating anaphylaxis and allowed for discontinuation of systemic glucocorticoids in two of three patients. The response pattern was not influenced by sex or mast cell clonality, but a complete response was reported more commonly among receivers of a higher omalizumab dose (≥300 mg/month). No major adverse events were reported. Conclusion: The majority of patients with refractory MCAS reported in the literature had a reduction in mast cell mediator-related symptoms with the addition of omalizumab.

Objective: To evaluate the association of parenteral epinephrine and terbutaline use on ventilatory support in children admitted to the intensive care unit (ICU) with critical asthma in the United States. Methods: Data were obtained from the Pediatric Health Information System data base for children ages 2 to 18 years admitted to the ICU with a diagnosis of asthma exacerbation from January 1, 2016, to December 31, 2023. The primary outcomes included noninvasive ventilation (NIV) and/or invasive mechanical ventilation (IMV) use after receipt of terbutaline and/or epinephrine. Secondary outcomes included serious adverse events from parenteral bronchodilators, including arrhythmias and elevated troponins. Results: Our study population included 53,328 patient encounters. Terbutaline and epinephrine were associated with decreased odds of subsequent NIV (terbutaline: odds ratio [OR] 0.52 [95% confidence interval {CI}, 0.44-0.63], p < 0.001; and epinephrine: OR 0.49 [95% CI, 0.43-0.55], p  < 0.001) and subsequent IMV (terbutaline: OR 0.51 [95% CI, 0.42-0.61], p < 0.001; and epinephrine: OR 0.34 [95% CI, 0.29-0.41], p < 0.001). There were no differences in adverse events in the terbutaline group when compared with the epinephrine group for both arrhythmia and elevated troponins (arrhythmia: terbutaline = 1.9%, epinephrine = 1.7%; p = 0.6; and elevated troponins: terbutaline = 0.1%, epinephrine = 0.1%, p  > 0.9). Conclusion: Parenteral bronchodilator use was associated with decreased odds of receiving subsequent ventilatory support in critical asthma. There were low rates of arrhythmia and elevated troponin overall. Our findings should inform future clinical trials to evaluate the use of parenteral bronchodilators in critical asthma in the United States.

Background: Cutaneous mastocytosis (CM) is the most common type of mastocytosis in children. The atopy frequency in these patients is typically similar to that in the general population, but a higher incidence of anaphylaxis is reported. Objective: This study aimed to evaluate the presence of allergic diseases in children diagnosed with CM and its impact on clinical manifestations. Methods: Children diagnosed with CM at Ankara Bilkent City Hospital Pediatric Allergy and Immunology Clinic between September 2019 and September 2023 were included in the study. Data, including demographic information, clinical details, and laboratory results, were gathered from medical records, encompassing personal and family allergy history. Results: The study included 58 patients (median [interquartile range{IQR}] age, 64 months [29-100.5 months]; 69% boys) with skin lesions as the primary concern. The median (IQR) age at which the lesions appeared was 9 months (3-39.25 months), and the median (IQR) age at hospital admission was 12 months (5- 50 months). The median (IQR) age at CM diagnosis was 13 months (6-53.5 months). The median (IQR) baseline tryptase value was 5.45 μg/L (3.93-9.00 μg/L), and 16 had an elevated tryptase value (>8 μg/L). Allergic diseases were present in 39.65% of the patients, with atopic dermatitis (18.9%) being the most common, followed by asthma (10.3%), allergic rhinitis (5.2%), food allergy (1.7%), and drug and bee venom allergies (1.7%). One patient had a history of anaphylaxis, diagnosed 4 months after consuming yogurt. A total of 18 patients, including this patient, were prescribed an adrenaline autoinjector. Conclusion: Various allergic diseases occurred in ∼40% of patients with CM and most commonly manifest as atopic dermatitis; 31% patients with risk factors for anaphylaxis were prescribed an adrenaline autoinjector.

Background: Standardized quality (SQ) house-dust mite (HDM) sublingual immunotherapy tablets (10,000 Japanese allergy units [JAU], equivalent to 6 SQ-HDM in Europe and the United States) are licensed for the treatment of HDMinduced allergic rhinitis (AR) without age restriction, based on 52-week administration clinical trials. There are no large-scale data on the administration of 10,000 JAU for > 1 year in actual clinical practice.

Objective: To examine the safety and effectiveness of 10,000 JAU during use for up to 3 years at real-world clinical sites in Japan.

Methods: This survey was a multicenter, observational, prospective study. We assessed the safety and effectiveness of the long-term administration of 10,000 JAU as well as effectiveness after its discontinuation in patients with HDM AR with an observation period of 3 years.

Results: The safety analysis included 815 patients, and the effectiveness analysis included 768 patients. Adverse reactionsthat occurred in 144 patients (17.67%) were mainly site-related events that occurred early in the dosing period. Seriousadverse reactions were dyspnea and anaphylactic reaction in one patient each, and both patients recovered. With regard toeffectiveness, compared with scores before the administration of SQ-HDM, nasal symptom scores decreased, depending on theadministration period, from 6 months to 3 years. Overall, 67.34% of the patients had improved quality of life after 6 months, and this improvement continued after 12 months. The proportion of patients with "improved and slightly improved" of overallimprovement exceeded 90% after 2 years. Treatment discontinuation because "symptoms disappeared" occurred in 24.42% of the patients at 3 years. Patients who discontinued 10,000 JAU (n = 39) had a sustained improvement in nasal symptomscores compared with baseline, even 1 year after discontinuing treatment.

Conclusion: The real-world safety and effectiveness of 10,000 JAU SQ-HDM sublingual immunotherapy tablets were confirmed in Japanese patients with HDM AR. No new safety and effectiveness precautions were required.

Patients and families living with food allergy may experience significant burdens, including social isolation, impaired quality of life, and anxiety. Allergists/immunologists play a critical role in educating families living with food allergies about risk, particularly with regard to the rarity of fatal food allergy. Appropriate risk framing can greatly decrease the fear-based burden of disease. In 2024, an increasing complex fabric of food allergy treatments has emerged that includes oral immunotherapy (OIT), sublingual immunotherapy (SLIT), and omalizumab, with the promise of additional treatments, including epicutaneous immunotherapy and oral mucosal immunotherapy in the near future. Younger children may be most likely to benefit from OIT and SLIT, with some evidence that suggests the possibility of an immunomodulatory effect. Omalizumab, approved in 2024 for use in conjunction with strict avoidance, increases the threshold of reactivity before a moderate-to-severe reaction for many, but not all, patients. There is no evidence to date that omalizumab has an immunomodulatory effect, and young children treated with omalizumab monotherapy may bear a lost opportunity cost from possible immunomodulation would they have been treated with OIT or SLIT instead; however, within a shared decision-making paradigm, beyond label use of omalizumab may include treatment with OIT or SLIT. Fortunately, the co-evolution of shared decision-making with modern food allergy treatments will facilitate the critical preference-sensitive care that must be characteristic of all decisions surrounding active food allergy management.

Background: Sulfonamides are associated with severe cutaneous adverse reactions (SCARs). Coronavirus disease 2019 (COVID-19) triggers an immune response, which may increase the likelihood of developing a hypersensitivity reaction. Objectives: We sought to explore the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the probability of developing SCARs and/or erythema multiforme (EM) reactions to sulfonamides. Methods: In the propensity score-matched cohort study by using the de-identified TriNetX Research data base, patients who had an exposure to antibiotic or non-antibiotic sulfonamides between March 1, 2020, and January 1, 2023, were divided into two groups based on the presence or absence of a previous COVID-19 infection within 6 months of starting the sulfonamide agent. The outcomes studied were the 30-day risk of developing SCARs or EM (Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, or EM) within 3 months of sulfonamide exposure. Cohorts were matched based on baseline demographics; malignant lymphoid neoplasms; human immunodeficiency virus; systemic lupus erythematosus; bone marrow transplantation; diabetes; psoriasis; seizures; gout; solid organ or stem cell transplantation; COVID-19 vaccination; and exposure to risk medications, including allopurinol, levetiracetam, carbamazepine, lamotrigine, oxcarbazepine, phenytoin, phenobarbital, abacavir, nevirapine, piroxicam, tenoxicam, or mexiletine. Results: When comparing 345,119 patients on sulfonamides and with previous COVID-19 to an equal number of sulfonamides users without a previous COVID-19, patients with COVID-19 had a lower risk of developing any form of SCARs (relative risk 0.39 [95% confidence interval, 0.26, 0.58]; p < 0.001). Conclusion: Previous SARS-CoV-2 infection seems to be associated with a lower probability of developing SCARs or EM among patients using sulfonamides.

Knowledge of the military regulations is key to guiding medical evaluations for applicants and service members. Military and civilian allergy consultants are often called on for their expertise to provide guidance with regard to the allergic conditions that may be potentially disqualifying from service per the published regulations for accession and retention. This review focuses on the role of the allergy consultant in military accession, retention, and deployments. To better understand and attempt to define the role of the allergy consultant in the process of medical evaluation for military applicants and for active duty service members, in the context of the ongoing national recruitment and force sustainment crisis, it is imperative to comprehend the intricacies of military accession and retention guidelines. Military medical standards guidelines are easy to access and should be used when evaluating applicants or active duty service members with allergic conditions. Medical documentation that aligns with military guidelines can help our patients streamline accession, retention, and waiver requests. The objective of this review is to provide a framework for how to address allergic concerns in the context of military service and apply accession and retention standards as indicated for patients who present with common allergic diagnoses.